The strategy of this program project has the assumption that deficits linked to schizophrenic vulnerability may be more useful than global clinical diagnostic variables in investigating genetic factors associated with that disorder. These vunerability-linked deficits tend to be identifiable (1) before, during, and after active episodes of schizophrenic illness, (2) in healthy first-degree relatives, and/or (3) in risk populations with personality traits suggestive of later schizophrenic breakdown. Another assumption is that better genetic understandings of schizophrenia may be obtained from comparative study of extended families with (a) multiple instances, (b) a single known instance, and (c) no instance of schizophrenic illness. Large pedigree families in these three categories will be examined on five schizophrenia-related deficits. Of these two are behavioral (reaction time crossover, span of apprehension with forced-choice/ partial-report procedure), two are biochemical (blood platelet, monoamine oxidase and plasma dopamine beta hydroxylase), and one is electrophysiological (visual evoked response augmenting/reducing measure). Each deficit measure will first be analysed independently of clinical symptoms of the family member. Once presence/absence segregation patterns have been established for each deficit, associative and linkage studies will be conducted. In addition to the genetics analyses, intercorrelated and group comparison of the deficit variables in the three types of families will be made. The sets of family members at extremes on the deficit variables will be examined blindly for individual clinical symptom variables (current and historic) and clinical diagnosis.